Arterial hypertension in a murine model of sleep apnea

Schulz, Richard; Murzabekova, G.; Egemnazarov, Bakytbek; Kraut, Simone; Eisele, Hans-Joachim; Dumitrascu, Rio; Heitmann, J.; Seimetz, Michael; Witzenrath, Martin; Ghofrani, Hossein Ardeschir; Schermuly, Ralph Theo; Grimminger, Friedrich; Seeger, Werner; Weißmann, Norbert

doi:10.1097/hjh.0000000000000016

Cited by 50 publications

(36 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reactive oxygen species (ROS) are the key factors promoting vascular injury in some cardiovascular diseases like hypertension and coronary artery disease [41][42][43]. Iron ions may be important independent source of ROS production.…”

Section: Discussionmentioning

confidence: 99%

HFE p.C282Y gene variant is associated with varicose veins in Russian population

et al. 2015

View full text Add to dashboard Cite

Recently, the association of polymorphism rs1800562 (p.C282Y) in the hemochromatosis (HFE) gene with the increased risk of venous ulceration was shown. We hypothesized that HFE gene polymorphism might be involved not only in ulceration process, but also in susceptibility to primary varicose veins. We genotyped HFE p.C282Y (rs1800562) and p.H63D (rs1799945) variants in patients with primary varicose veins (n = 463) and in the control group (n = 754). In our study, p.282Y variant (rs1800562 A allele) was significantly associated with the risk of varicose veins (OR 1.79, 95 % CI = 1.11-2.89, P = 0.02). A borderline significant reverse association of p.63D variant (rs1799945 G allele) with venous leg ulcer development was revealed in Russians (OR 0.25, 95 % CI = 0.06-1.00, P = 0.05), but not in the meta-analysis (P = 0.56). We conclude that the HFE gene polymorphism can affect the risk of developing primary varicose veins.

show abstract

Section: Discussionmentioning

confidence: 99%

HFE p.C282Y gene variant is associated with varicose veins in Russian population

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The role of NOXs has been addressed in different animal models of PH such as persistent PH of the newborn in foetal lambs [27], chronic intermittent hypoxia-induced PH in mice [151], monocrotaline-induced PH in rats [179] and, importantly, in chronic hypoxia-induced PH in newborn piglets [39] and in mice [112].…”

Section: Noxs and Chronic Hypoxia-induced Pulmonary Hypertensionmentioning

confidence: 99%

NADPH oxidases—do they play a role in TRPC regulation under hypoxia?

Malczyk

Veith

Schermuly

et al. 2015

Pflugers Arch - Eur J Physiol

Self Cite

View full text Add to dashboard Cite

In the lung, acute alveolar hypoxia causes hypoxic pulmonary vasoconstriction (HPV) to maintain ventilation perfusion matching and thus optimal oxygenation of blood. In contrast, global chronic hypoxia triggers a pathological thickening of pulmonary arterial walls, called pulmonary vascular remodelling, leading to persistence of pulmonary hypertension (PH). Moreover, ischaemia or hypoxia can lead to a damage of pulmonary endothelial cells with subsequent oedema formation. Alterations in reactive oxygen species (ROS) have been suggested as a crucial mediator of such responses. Among the various sources of cellular ROS production, NADPH oxidases (NOXs) have been found to contribute to these physiological and pathophysiological signalling processes. NOXs are the only known examples that generate ROS as the primary function of the enzyme system. However, the downstream targets of NOX-derived ROS signalling in hypoxia are still not known. Canonical transient receptor potential (TRPC) channels recently have been recognised as directly or indirectly ROS-activated channels and have been shown to be essential for hypoxia-dependent vascular regulatory processes in the lung. Against this background, we here summarise the current knowledge on NOX-mediated TRPC channel signalling during hypoxia in the pulmonary circulation.

show abstract

“…There is a sizeable discrepancy regarding the duration of IH cycles, ranging from 120 cycles/h (30 s cycle; Fletcher et al, 1992a; Julien et al, 2003; Dematteis et al, 2008), 80 cycles/h (6 min cycle; Knight et al, 2011), 60 cycles/h (1 min cycle; Campen et al, 2005), and when the chambers are larger, longer cycles are often used, reducing the number of cycles/h (Zoccal et al, 2007, 2008; Silva and Schreihofer, 2011) of daytime exposure, from 4 h/day (Kalaria et al, 2004), 6 h/day (Lai et al, 2006), 7 h/day (Fletcher et al, 1992a), 8 h/day (Chen et al, 2005; Belaidi et al, 2009; Zoccal et al, 2008, 2009; Knight et al, 2011; Silva and Schreihofer, 2011; Dyavanapalli et al, 2014; Schulz et al, 2014), 10 h/day (Liu et al, 2013) to 12 h/day (Lin et al, 2007). The exposure duration of 8 h/day seems to be that on which there is the greatest consensus (see Table 2).…”

Section: What Models Are Available To Study Ht Related To Osa?mentioning

confidence: 99%

“…It is apparent that arterial catheterization is not an accurate method of measuring BP in CIH models. The methods most often used for BP measurement (for a review, see Kurtz et al, 2005) in IH models (see Table 2) are the tail-cuff method (Allahdadi et al, 2005; Chen et al, 2005; Soukhova-O'Hare et al, 2008; Belaidi et al, 2009; Totoson et al, 2013), radiotelemetry (Fletcher, 2000; Tahawi et al, 2001; Lai et al, 2006; Knight et al, 2011; Bathina et al, 2013; Sharpe et al, 2013; Dyavanapalli et al, 2014; Schulz et al, 2014), and arterial catheterization (Kanagy et al, 2001; Kalaria et al, 2004; Campen et al, 2005; Lin et al, 2007; Belaidi et al, 2009; Zoccal et al, 2009; Iturriaga et al, 2010; Perry et al, 2011; Silva and Schreihofer, 2011; Totoson et al, 2013). …”

Section: What Models Are Available To Study Ht Related To Osa?mentioning

confidence: 99%

“…The study undertaken by Bathina et al revealed that the knockdown of tyrosine hydroxylase in the nucleus of the solitary (NTS) tract reduces the CIH-induced persistent increase in MAP, suggesting that noradrenergic A 2 neurons in nucleus tractus solitarius play a role in the cardiovascular responses to CIH (Bathina et al, 2013). More recently, Schulz et al have shown that NADPH oxidase 2 (NOX2) knockout blocks the development of HT induced by CIH, suggesting that this type of HT is mediated by reactive oxygen species (ROS) derived from the activation of NOX2 within cells located outside the cardiovascular system (Schulz et al, 2014). …”

Section: What Are the Mechanisms Involved In The Pathogenesis Of Ht Rmentioning

confidence: 99%

See 1 more Smart Citation

The efficacy of antihypertensive drugs in chronic intermittent hypoxia conditions

Diogo

Monteiro

2014

Front. Physiol.

View full text Add to dashboard Cite

Sleep apnea/hypopnea disorders include centrally originated diseases and obstructive sleep apnea (OSA). This last condition is renowned as a frequent secondary cause of hypertension (HT). The mechanisms involved in the pathogenesis of HT can be summarized in relation to two main pathways: sympathetic nervous system stimulation mediated mainly by activation of carotid body (CB) chemoreflexes and/or asphyxia, and, by no means the least important, the systemic effects of chronic intermittent hypoxia (CIH). The use of animal models has revealed that CIH is the critical stimulus underlying sympathetic activity and hypertension, and that this effect requires the presence of functional arterial chemoreceptors, which are hyperactive in CIH. These models of CIH mimic the HT observed in humans and allow the study of CIH independently without the mechanical obstruction component. The effect of continuous positive airway pressure (CPAP), the gold standard treatment for OSA patients, to reduce blood pressure seems to be modest and concomitant antihypertensive therapy is still required. We focus this review on the efficacy of pharmacological interventions to revert HT associated with CIH conditions in both animal models and humans. First, we explore the experimental animal models, developed to mimic HT related to CIH, which have been used to investigate the effect of antihypertensive drugs (AHDs). Second, we review what is known about drug efficacy to reverse HT induced by CIH in animals. Moreover, findings in humans with OSA are cited to demonstrate the lack of strong evidence for the establishment of a first-line antihypertensive regimen for these patients. Indeed, specific therapeutic guidelines for the pharmacological treatment of HT in these patients are still lacking. Finally, we discuss the future perspectives concerning the non-pharmacological and pharmacological management of this particular type of HT.

show abstract

Arterial hypertension in a murine model of sleep apnea

Abstract: We suggest that the CIH-induced arterial hypertension is mediated by ROS derived from an activation of NOX2 within cells located outside the cardiovascular system.

Cited by 50 publications

References 33 publications

HFE p.C282Y gene variant is associated with varicose veins in Russian population

HFE p.C282Y gene variant is associated with varicose veins in Russian population

NADPH oxidases—do they play a role in TRPC regulation under hypoxia?

The efficacy of antihypertensive drugs in chronic intermittent hypoxia conditions

Contact Info

Product

Resources

About